1. Field of Invention
The invention relates to an apparatus and method for perfusing one or more organs or tissue (hereinafter generally referred to as organs) to monitor, sustain and/or restore the viability of the organ(s) and/or for transporting and/or storing the organ(s). This invention further relates to perfusing an organ with a second perfusion fluid to introduce a substance into the organ and create a reaction between the organ and the substance to facilitate further studies on and/or with the organ.
2. Description of Related Art
Preservation of organs by machine perfusion has been accomplished at hypothermic temperatures with or without computer control with crystalloid perfusates and without oxygenation. Hypothermic temperatures provide a decrease in organ metabolism, lower the energy requirements, delay the depletion of high energy phosphate reserves and accumulation of lactic acid and retard the morphological and functional deterioration associated with disruption of blood supply. Oxygen can not be utilized efficiently by mitochondria below approximately 20° C. to produce energy, and the reduction in catalase/superoxide dismutase production and ascorbyl and glutathione regeneration at low temperatures allows high free radical formation. The removal of oxygen from perfusates during low temperature machine perfusion has even proven helpful in improving organ transplant results by some investigators.
Reduction in potential oxygen damage is also accomplished via the addition of antioxidants to the perfusate. In particular, this has proven useful in reducing organ damage after long warm ischemia times. Numerous other perfusate additives have also been reported to improve the outcome of machine perfusion.
Ideally organs would be procured in a manner that limits their warm ischemia time to essentially zero. Unfortunately, in reality, many organs, especially from non-beating heart donors, are procured after extended warm ischemia time periods (i.e., 45 minutes or more). The machine perfusion of these organs at low temperature has demonstrated significant improvement. However, in some situations the use of such pumps for machine perfusion of organs may increase the risk of overpressurization of the organ should the organ perfusion apparatus malfunction. High pressure perfusion (e.g., above about 60 mm Hg) can wash off the vascular endothelial lining of the organ and in general damages organ tissue, in particular at hypothermic temperatures where the organ does not have the neurological or endocrinal connections to protect itself by dilating its vasculature under high pressure.
While machine preservation of organs intended for transplantation has been established, it has not been historically used in clinical settings for certain organs, such as the pancreas. The fear of swelling of the organ, called edema, and thus, possibly impairing the good function of the entire organ has prevented the use of machine preservation of organs. Thus, the prior art has addressed the need to restore or maintain an organ's physiological function after preservation for an extended period of time without using machine preservation. For example, a pancreas can be preserved in static storage in UW solution for a maximum of 16 hours.
However, concerns about machine preservation of the organs such as pancreas, and the resulting problems, specifically edema, are no longer as significant in view of the recent success of an alternative to whole-organ transplantation, such as transplantation of just the cluster of cells found in the pancreas known as islets. The islets account for about 2% of the mass of the pancreas's tissue and contain beta cells which produce insulin. Insulin is needed for proper metabolism in diabetic patients. Transplantation of the whole pancreas complicates and extends the time of surgery, thus increasing risk to the patient. As islets are the primary and possibly only part of the pancreas that is required to cure diabetes, an alternative solution is to isolate the islets from the pancreas and transplant those alone.
Transplantation of the islets involves separating the insulin-producing parts (endocrine parts) of the donor pancreas from the digestive (exocrine parts), fibrous, and vascular parts, and then transplanting only the insulin-producing parts (the islets) as into the donee's portal vein of the liver or elsewhere. Islet separation has several advantages compared to whole-organ transplantation, including minimum trauma to the recipient while providing the potential of curing the patient.
The state of the art of islet separation involves the following general steps: 1) distention; 2) digestion; and 3) purification. However, these existing steps are conducted manually, for example manually injecting a substance into the pancreas during the distention step. Further the steps are tedious taking 2 or more persons 8 or more hours to perform. An additional complication for the steps above is that in order to gather a suitable and healthy supply of islets, the pancreas should be maintained in aseptic and hypothermic conditions from removal of the pancreas from the donor to the steps of isolating the islets from the pancreas.